Impaired cerebrovascular hemodynamics are associated with cerebral white matter damage

Abstract

White matter hyperintensities (WMH) in elderly individuals with vascular diseases are presumed to be due to ischemic small vessel diseases; however, their etiology is unknown. We examined the cross-sectional relationship between cerebrovascular hemodynamics and white matter structural integrity in elderly individuals with vascular risk factors. White matter hyperintensity volumes, fractional anisotropy (FA), and mean diffusivity (MD) were obtained from MRI in 48 subjects (75±7years). Pulsatility index (PI) and dynamic cerebral autoregulation (dCA) was assessed using transcranial Doppler ultrasound of the middle cerebral artery. Dynamic cerebral autoregulation was calculated from transfer function analysis (phase and gain) of spontaneous blood pressure and flow velocity oscillations in the low (LF, 0.03 to 0.15 Hz) and high (HF, 0.16 to 0.5 Hz) frequency ranges. Higher PI was associated with greater WMH (P<0.005). Higher phase across all frequency ranges was associated with greater FA and lower MD (P<0.005). Lower gain was associated with higher FA in the LF range (P=0.001). These relationships between phase and FA were significant in the territories limited to the middle cerebral artery as well as across the entire brain. Our results show a strong relationship between impaired cerebrovascular hemodynamics (PI and dCA) and loss of cerebral white matter structural integrity (WMH and DTI metrics) in elderly individuals.

Figures

Figure 1

Distribution and frequency of white matter hyperintensities (WMH). The figure visually illustrates the distribution and frequency of WMH obtained from brain images of all subjects. The map was obtained after normalization of all the individual WMH maps to a common space (a reference brain described previously). The WMH frequency map (color) is shown overlaid onto a reference brain (gray scale). The colors represent the percentage (%) of subjects with WMH at a given anatomic location. The color code is illustrated by the color bar on the right. Panels show four different levels (slices), each 10 mm apart in axial view (left to right: more superior parts of the brain). Top and bottom of figure correspond to anterior and posterior of the brain, respectively. The results show a predominantly periventricular distribution of the WMH, especially around the anterior and posterior horns of the ventricles. In some cases, WMH is also present in deep white matter areas.

Figure 2

Relationship between dynamic cerebral autoregulation and fractional anisotropy (FA) and mean diffusivity (MD) in normal-appearing white matter. Transfer function phase and gain are plotted across the frequency spectrum of 0 to 0.5 Hz in subjects with low and high (divided at the median) fractional anisotropy (FA, median=0.395, range=0.319 to 0.478) and mean diffusivity (MD, median=0.814, range=0.716 to 1.061) in regions of normal-appearing white matter. Solid blue and dashed red lines indicate mean phase and gain across the frequency range for high and low FA and MD, respectively, and the shaded regions are standard error of the mean (s.e.m.). Low FA and high MD represent lower white matter structural integrity and lower phase and higher gain values indicate less effective dynamic cerebral autoregulation.

Figure 3

Relationship between dynamic cerebral autoregulation and fractional anisotropy in normal-appearing white matter in the middle cerebral artery territory and whole brain. Scatterplots illustrate the relationship between transfer function phase or gain and fractional anisotropy in normal-appearing white matter supplied by the middle cerebral artery (MCA region), normal-appearing white matter not supplied by the MCA (non-MCA regions) and the whole brain normal-appearing white matter (Global). The shaded region in each graph represents the 95% confidence intervals of the linear prediction line. r=correlation coefficient; P=alpha level of significance.